OVERVIEW: What every practitioner needs to know
Are you sure your patient has cat scratch disease? What are the typical findings for this disease?
The most common clinical manifestation of cat scratch disease (CSD) is chronic lymphadenopathy. The affected node is often warm, tender, and erythematous (See Figure 1). Fever occurs in approximately half of patients and systemic symptoms such as fatigue, malaise, anorexia, and headache may occur and are generally mild. Most patients (approximately 50-85%) have only single node involvement, with the axillary and epitrochlear, head and neck, and inguinal nodes most commonly affected.
While this “classic” presentation is most common, CSD also can present with a variety of “atypical” clinical manifestations, including prolonged fever/fever of unknown origin (FUO), hepatosplenic disease, encephalopathy/encephalitis, osteomyelitis, endocarditis, and ocular disease. Immunocompromised patients, such as those with AIDS, may present with hemangioma-like skin lesions (bacillary angiomatosis) that may be accompanied by disseminated disease (peliosis) involving the liver or spleen.
What other disease/condition shares some of these symptoms?
The differential diagnosis of cat scratch lympadenopathy includes other causes of subacute or chronic lymphadenopathy. Primarily, this means other granulomatous infections such as Mycobacterium tuberculosis as well as non-tuberculous mycobacteria, fungi, nocardia, and actinomyces. Non-infectious diseases that may present with similar manifestations include malignancies and autoimmune diseases. In the first few days of illness, the differential diagnosis includes acute bacterial lymphadenitis.
What caused this disease to develop at this time?
After inoculation of the bacteria via a cat scratch, patients often develop an erythematous papule 3 to 10 days later at the site of the scratch. They then may develop regional lymphadenopathy 1 to 3 weeks after inoculation.
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
Laboratory studies usually are not needed in a patient with classic disease and an epidemiologic history that includes contact with a cat (particularly if the patient was scratched by a kitten). Laboratory confirmation of the diagnosis can be challenging, as the sensitivity and specificity of serologic tests (such as an indirect fluoresence assay or enzyme immunoassay), which are the standard method of diagnosis, are variable. It is important to emphasize that a negative antibody test result does not exclude the diagnosis, especially early in the clinical course.
Histopathology of infected lymph nodes demonstrates granulomatous inflammation with areas of focal necrosis and microabscesses. Bacilli can sometimes be visualized using the Warthin Starry or another silver stain.
Bartonella henselae, the cause of CSD, can be isolated from the blood of immunocompromised patients with bacillary angiomatosis, but blood cultures from patients with endocarditis are rarely positive. Culturing the bacteria from lymph nodes, liver, or spleen is possible but the organism is fastidious, special media and techniques are necessary to enhance the likelihood of recovering the organism, and 2 to 6 weeks may be required for isolation.
Polymerase chain reaction (PCR) can be used to identify the bacteria from tissue specimens, pus, or skin lesions.
Would imaging studies be helpful? If so, which ones?
Imaging studies usually are not necessary for patients with cat scratch lympadenopathy.
In patients with FUO or suspected hepatosplenic disease, an imaging study of the abdomen (ultrasound or CT scan) may be useful to identify microabscesses of the liver and/or spleen.
Children with suspected osteomyelitis should be evaluated with appropriate imaging studies to make that diagnosis.
Confirming the diagnosis
The keys to making a diagnosis are to obtain the history of cat exposure (which, unfortunately, is not present in all patients) and to recognize that the clinical presentation may be a manifestation of CSD.
If you are able to confirm that the patient has cat scratch disease, what treatment should be initiated?
The role of antimicrobial therapy in the management of patients with cat scratch disease remains ill defined. In general, CSD is a self-limited disease and antimicrobial therapy is not recommended for most patients with mild-to-moderate disease. For patients with complicated or more severe disease, such as retinitis or hepatosplenic disease, therapy is often adminstered using one or two agents.
The optimal agent(s) for therapy of cat scratch disease remains uncertain because there is significant discordance between in vitro antimicrobial susceptibilities and apparent clinical effectiveness. In addition, most clinical data derive from retrospective reviews and cases series. In one prospective randomized trail of azithromycin vs. placebo, azithromycin-treated patients had a significant decrease in lymph node size at 30 days, but there was no significant decrease thereafter.
Among the agents that may be effective and are commonly used are azithromycin, trimethoprim-sulfamethoxazole, rifampin, gentamicin, ciprofloxacin, and doxycycline.
Patients with retinitis are often treated with doxcycline because of the drug’s excellent intraocular penetration.
Patients with bacillary angiomatosis or peliosis are treated with erythromycin or doxycycline and respond rapidly to antibiotic therapy.
What are the possible outcomes of cat scratch disease?
Cat scratch disease is a self-limited disease that resolves without sequelae in the vast majority of cases, although resolution can take up to 2 to 6 months.
The prognosis for patients with CSD encephalopathy is generally excellent, with over 90% recovering completely without sequelae. Similarly, the prognosis for patients with retinitis or osteomyelitis is excellent, often in the absence of specific antimicrobial therapy, although various antibiotic regimens are frequently prescribed.
What causes this disease and how frequent is it?
Cat scratch disease is caused by Bartonella henselae, a fastidious, slow-growing Gram-negative bacilllus. The organism is transmitted from cats (and, rarely, dogs) to humans via scratches, licks, and bites. Approximately 40% of cats are asymptomatically infected (and even bacteremic) with B. henselae at some point in their lives, and kittens and outdoor cats are more likely to be infected. Cat fleas play an important role in transmitting the organism among cats, but their role in transmitting the infection to humans in unclear. Nonetheless, epidemiologic studies suggest that contact with flea-infested kittens increases the risk of CSD.
It has been estimated that 22,000 cases occur annually in the United States, but the true incidence is unknown since many cases are not diagnosed and CSD is not a reportable disease. Although CSD occurs in persons of all ages, the vast majority of cases occur in children younger than 10 years of age. CSD is more common in the fall and winter months for reasons that are unclear, but may reflect seasonal fluctuations in transmission of the organism among cats or in animal behavior.
Other clinical manifestations that might help with diagnosis and management
Patients with atypical presentations of CSD may not present with regional lymphadenopathy; therefore, obtaining a history of cat/kitten exposure is critical in considering the diagnosis.
CSD is increasingly recognized as a fairly common cause of FUO in children and the diagnosis should be considered in any child with prolonged fever who has contact with cats. Abdominal pain may be a presenting complaint in these patients.
Children with hepatosplenic CSD usually present with prolonged fever, with or without abdominal pain. Patients may also have chills, headaches, and weight loss. Abdominal pain is usually intermittent. Physical examination may reveal enlargement of the liver and/or spleen, and lymphadenopathy is present in only some patients. Laboratories are significant for marked elevation of acute phase reactants and liver enzymes are often normal. Radiologic evaluation with ultrasound or CT scan reveals multiple microabscesses of the liver, spleen, or both.
Encephalitis/encephalopathy is a rare manifestation of CSD and children present with neurologic findings that may include headaches, altered mental status, and seizures (including status epilepticus). Findings on physical examination may include meningismus, weakness, and hypo- or hyperreflexia. A lumbar puncture may reveal a CSF pleocytosis and elevated protein, although in most cases the results are normal.
Osteomyelitits is another rare manifestation of CSD and presents subacutely. Various sites of infection have been reported, but vertebral osteomyelitis appears to be most common and multi-focal bone involvement has also been described. Patients usually present with bone pain and fever and may have markedly elevated acute phase reactants.
Parinaud’s oculoglandular syndrome, which consists of unilateral eye redness with serous or purulent conjunctivitis and ipsalteral lympadenopathy, is the most common ocular manifestation of CSD. Patients with ocular disease may present with acute visual loss from neuroretinitis (characterized by optic disk edema, often with a partial or complete macular star) or retinochoroiditis.
Endocarditis is a very rare complication of CSD in children. It presents subacutely and has been reported in children with underlying valvular disease.
Immunocompromised patients may present with potentially life-threatening manifestations, such as bacillary angiomatosis and peliosis. Children with the latter condition present with fever, chills, gastrointestinal symptoms, and hepatosplenomegaly.
What complications might you expect from the disease or treatment of the disease?
Most infections resolve without sequelae, although recovery can be prolonged.
How can cat scratch disease be prevented?
Prevention of CSD includes elimination of cat fleas from cats and avoidance of traumatic injury from cats, which is particularly important for immunocompromised patients. Infected cats are usually asymptomatic and there are no commercially available vaccines to prevent B. henselae infection among cats.
What is the evidence?
Florin, TA, Zaoutis, TE, Zaoutis, LB. “Beyond cat scratch disease: widening spectrum of infection”. . vol. 121. 2008. pp. e1413-25. (Excellent review of CSD focusing primarily on atypical presentations.)
Arisoy, ES, Correa, AG, Wagner, ML, Kaplan, SL. “Hepatosplenic cat scratch disease in children: selected clinical features and treatment”. Clin Infect Dis. vol. 28. 1999. pp. 778-84. (Case series of 19 children with hepatosplenic CSD seen at Texas Children's Hospital.)
Hajjaji, N, Hocqueloux, L, Kerdraon, R, Bret, L. “Bone infection in cat-scratch disease: a review of the literature”. . vol. 54. 2007. pp. 417-421. (Review of the clinical features, treatment, and outcome of 47 patients with CSD osteomyeletis described in the medical literature.)
Rolain, JM, Broqui, P, Koehler, JE, Maguina, C, Dolan, MJ, Raoult, D. “Recommendations for treatment of human infections caused by Bartonella species”. Antimicrob Agents Chemother. vol. 48. 2004. pp. 1921-1933. (Recommendations for use of antimicrobial agents for various manifestations of CSD, which, unfortunately, highlight the paucity of good data upon which to base recommendations. The major conclusion is that antimicrobial therapy is not recommended for most immunocompetent patients with mild-to-moderate disease because it is not clear that such therapy is useful and because of the risk of adverse drug reactions.)
Bass, JW, Freitas, BC, Freitas, AD. “Prospective randomnized double blind placebo-controlled evaluation of azithromycin for treatment of cat-scratch disease”. Pediatr Infect Dis J. vol. 17. 1998. pp. 447-452. (Only such trial to be performed in immunocompetent patients with classic CSD showed 80% improvement in lymph node size in 7 of 14 treated patients but only 1 of 15 untreated patients at 30 days, but no significant differences thereafter.)
Ongoing controversies regarding etiology, diagnosis, treatment
The major ongoing controversy is the role of antimicrobial therapy in the management of immunocompetent patients with the various forms of CSD, as there are insufficient data to define the conditons that may benefit from therapy and to determine the best agent(s) to use.
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- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has cat scratch disease? What are the typical findings for this disease?
- What other disease/condition shares some of these symptoms?
- What caused this disease to develop at this time?
- Would imaging studies be helpful? If so, which ones?
- Confirming the diagnosis
- If you are able to confirm that the patient has cat scratch disease, what treatment should be initiated?
- What are the possible outcomes of cat scratch disease?
- What causes this disease and how frequent is it?
- Other clinical manifestations that might help with diagnosis and management
- What complications might you expect from the disease or treatment of the disease?
- How can cat scratch disease be prevented?
- What is the evidence?
- Ongoing controversies regarding etiology, diagnosis, treatment